文献类型：期刊文献

英文题名：Downregulation of miR-155-5p enhances the anti-tumor effect of cetuximab on triple-negative breast cancer cells via inducing cell apoptosis and pyroptosis

作者：Xu, Wen[1,2];Song, Changfeng[1,2];Wang, Xiaotong[1,2];Li, Yueqi[1,2];Bai, Xue[1,2];Liang, Xin[1,2];Wu, Jingjing[3];Liu, Jianwen[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China;[2]Shanghai Key Lab New Drug Design, East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[3]Shanghai Univ TCM, Dept Breast, Longhua Hosp, Shanghai 200032, Peoples R China

年份：2021

卷号：13

期号：1

起止页码：228

外文期刊名：AGING-US

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000611152600015)】；

基金：Supported by National Natural Science Foundation of China (81803082), and China postdoctoral Science Foundation (2018M632046).

语种：英文

外文关键词：triple-negative breast cancer; microRNA 155-5p; cetuximab; apoptosis; pyroptosis

摘要：Cetuximab resistance is the main obstacle for the treatment of EGFR overexpression cancer, including triple negative breast cancer (TNBC). MicroRNA (miRNA)-155-5p is upregulated in TNBC cells; thus, the present study explored whether the downregulation of miR-155-5p enhanced the anti-tumor effect of cetuximab in TNBC cells. MDA-MB-231 and MDA-MB-468 cells were infected with lentivirus-epidermal growth factor receptor (EGFR) for 72 h to obtain EGFR-overexpressed cell lines (MDA-MB-231 and MDA-MB-468). The inhibitory effects of cetuximab on the proliferation and migration of EGFR-overexpressed MDA-MB-468 cells were enhanced following transfection with the miR-155-5p antagomir, and miR-155-5p knockdown enhanced the pro-apoptotic effect of cetuximab on EGFR-overexpressed MDA-MB-468 cells. Further, the luciferase reporter assay revealed that gasdermin E (GSDME) was the direct binding target of miR-155-5p. The combination of cetuximab with the miR-155-5p antagomir promoted pyroptosis in EGFR-overexpressed MDA-MB-468 cells via the upregulation of GSDME-N and cleaved caspase-1. Results from the in vivo experiments confirmed that the downregulation of miR-155-5p enhanced the anti-tumor effect of cetuximab in an MDA-MB-468 xenograft model and on EGFRoverexpressed TNBC cells via inducing cell apoptosis and pyroptosis. Therefore, cetuximab combination with an miR-155-5p antagomir may be a novel therapeutic strategy for the treatment of TNBC.